Accuracy of Pneumocystis jirovecii Plasma Cell-Free DNA PCR for Noninvasive Diagnosis of Pneumocystis Pneumonia

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is a serious infection in immunocompromised hosts which requires prompt diagnosis and treatment. The recommended specimen for diagnosis of PCP is bronchoalveolar lavage (BAL) fluid, which is invasive and may not be possible in unstable patients. The aim of this study was to evaluate the accuracy of noninvasive P. jirovecii plasma cell-free DNA (cfDNA) PCR using recently optimized preanalytical and analytical methods. Adult patients undergoing clinical testing for PCP with direct fluorescent antibody stain (DFA), respiratory PCR, and/or beta-D-glucan were included in this study. Sensitivity and specificity P. jirovecii plasma cfDNA PCR was determined in PCP suspects categorized as proven and probable. A total of 149 patients were included in this study, of which 10 had proven and 27 had probable PCP. Most patients (95.9%, 143/149) were immunocompromised, including hematological malignancies (30.1%), bone marrow transplant (11.2%), solid organ transplantation (47.6%), and HIV/AIDS (4.2%). P. jirovecii plasma cfDNA PCR showed sensitivity and specificity of 100% (10/10; 95% confidence interval [CI], 69.2 to 100) and 93.4% (127/136; 95% CI, 87.8 to 96.9), and 48.6% (18/37; 95% CI, 31.9 to 65.6) and 99.1% (108/109; 95% CI, 94.9 to 100) in proven and proven/probable cases, respectively. P. jirovecii cell-free DNA PCR was similar in sensitivity but with substantially improved specificity over beta-D-glucan (sensitivity, 60.0% [18/30; 95% CI, 40.6 to 77.3]); specificity, 66.7% [22/33; 95% CI, 48.2 to 82.0]) in patients with proven/probable PCP. Plasma cfDNA PCR offers a noninvasive testing option for early and accurate diagnosis of PCP, particularly in patients who cannot tolerate bronchoscopy.